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Clozapine is recognized as the gold standard for treating treatment-resistant schizophrenia but carries a notable risk of severe adverse effects. This case report presents a 61-year-old Welsh woman with paranoid schizophrenia and epilepsy who, while on long-term clozapine and valproic acid therapy, developed a progressive decline in mobility, cognition, and social engagement, punctuated by recurrent falls. Despite numerous hospital visits and extensive investigations, the underlying cause of her symptoms remained elusive until serum clozapine level testing revealed toxicity, with levels significantly exceeding the therapeutic range. Following the gradual tapering and ultimate cessation of clozapine, the patient exhibited marked improvements in both mobility and cognitive function. This case highlights the potential utility of serum level monitoring in patients on clozapine, especially those showing unexplained deterioration in mobility and social engagement, as toxicity can arise even after prolonged stable treatment. The findings emphasize the necessity for vigilant monitoring and proactive management strategies to mitigate the risk of severe neurological complications associated with clozapine therapy.
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http://dx.doi.org/10.7759/cureus.79771 | DOI Listing |
JCI Insight
September 2025
Division of Nephrology, Boston University Chobanian & Avedisian School of Medicine, Boston, United States of America.
Background: Active vitamin D metabolites, including 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D), have potent immunomodulatory effects that attenuate acute kidney injury (AKI) in animal models.
Methods: We conducted a phase 2, randomized, double-blind, multiple-dose, 3-arm clinical trial comparing oral calcifediol (25D), calcitriol (1,25D), and placebo among 150 critically ill adult patients at high-risk of moderate-to-severe AKI. The primary endpoint was a hierarchical composite of death, kidney replacement therapy (KRT), and kidney injury (baseline-adjusted mean change in serum creatinine), each assessed within 7 days following enrollment using a rank-based procedure.
J Clin Invest
September 2025
The University of Texas at Austin, Austin, United States of America.
Background: Following SARS-CoV-2 infection, ~10-35% of COVID-19 patients experience long COVID (LC), in which debilitating symptoms persist for at least three months. Elucidating biologic underpinnings of LC could identify therapeutic opportunities.
Methods: We utilized machine learning methods on biologic analytes provided over 12-months after hospital discharge from >500 COVID-19 patients in the IMPACC cohort to identify a multi-omics "recovery factor", trained on patient-reported physical function survey scores.
JAMA Netw Open
September 2025
Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Importance: Exposure to inflammation from chorioamnionitis places the fetus at higher risk of premature birth and may increase the risk of neurodevelopmental impairments, though the evidence for the latter is mixed.
Objective: To evaluate whether moderate to severe histologic chorioamnionitis (HCA) is directly associated with adverse motor performance, independent of the indirect mediating effects of premature birth.
Design, Setting, And Participants: This prospective, population-based cohort study recruited participants between September 16, 2016, and November 19, 2019, from referral and nonreferral neonatal intensive care units of 5 southwestern Ohio hospitals.
J Gambl Stud
September 2025
Department of Psychology and Azrieli Israel Center for Addiction and Mental Health, The Hebrew University of Jerusalem, Jerusalem, Israel.
Research suggests that Problem Gambling (PG) may result from maladaptive emotional regulation strategies aimed at escaping emotions and stress caused by negative life events and trauma. The current study, aimed to examine the effect of exposure to the mass trauma of October 7, 2023 terror attack and the consequent Swords of Iron war in Israel, and difficulties in emotional regulation on PG. We utilized longitudinal data of self-reports in the Problem Gambling Severity Index collected before the terror attack (April 2022) and during the Swords of Iron war (December 2023, March 2024, June 2024; N = 899) from a large sample of adult Jewish Israelis.
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September 2025
Neuroscience Research Australia, University of New South Wales, Sydney, Australia.
Objectives: Patients diagnosed with amyotrophic lateral sclerosis (ALS) typically describe symptoms of fatigue. Despite this frequency, the underlying mechanisms of fatigue are poorly understood, and are likely multifactorial. To help clarify mechanisms, the present systematic review was undertaken to determine the risk factors related to fatigue in ALS.
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